Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy
| Autor: | Weiping Zou, Ta Chung Yu, Nisha Nagarsheth, Ji-Xuan Han, Dan Ma, Fangfang Guo, Jie Hong, Yun Qian, Haoyan Chen, Ya-Nan Yu, Ilona Kryczek, Danfeng Sun, Tian-Tian Sun, Ying-Xuan Chen, Jing-Yuan Fang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Colorectal cancer Antineoplastic Agents Platinum Compounds Mouse model of colorectal and intestinal cancer Biology Gut flora medicine.disease_cause General Biochemistry Genetics and Molecular Biology Mice 03 medical and health sciences 0302 clinical medicine stomatognathic system Recurrence microRNA Autophagy Tumor Microenvironment medicine Animals Capecitabine Toll-like receptor Fusobacterium nucleatum Toll-Like Receptors medicine.disease biology.organism_classification Gastrointestinal Microbiome MicroRNAs stomatognathic diseases 030104 developmental biology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Immunology Cancer research Heterografts Colorectal Neoplasms Carcinogenesis Neoplasm Transplantation |
| Zdroj: | Cell. 170:548-563.e16 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2017.07.008 |
| Popis: | Gut microbiota are linked to chronic inflammation and carcinogenesis. Chemotherapy failure is the major cause of recurrence and poor prognosis in colorectal cancer patients. Here, we investigated the contribution of gut microbiota to chemoresistance in patients with colorectal cancer. We found that Fusobacterium (F.) nucleatum was abundant in colorectal cancer tissues in patients with recurrence post chemotherapy, and was associated with patient clinicopathological characterisitcs. Furthermore, our bioinformatic and functional studies demonstrated that F. nucleatum promoted colorectal cancer resistance to chemotherapy. Mechanistically, F. nucleatum targeted TLR4 and MYD88 innate immune signaling and specific microRNAs to activate the autophagy pathway and alter colorectal cancer chemotherapeutic response. Thus, F. nucleatum orchestrates a molecular network of the Toll-like receptor, microRNAs, and autophagy to clinically, biologically, and mechanistically control colorectal cancer chemoresistance. Measuring and targeting F. nucleatum and its associated pathway will yield valuable insight into clinical management and may ameliorate colorectal cancer patient outcomes. |
| Databáze: | OpenAIRE |
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